Mass spectrometry imaging (MSI) is a powerful tool that enables untargeted investigations into the spatial distribution of molecular species in a variety of samples. It has the capability to image thousands of molecules, such as metabolites, lipids, peptides, proteins, and glycans, in a single experiment without labeling. The combination of information gained from mass spectrometry (MS) and visualization of spatial distributions in thin sample sections makes this a valuable chemical analysis tool useful for biological specimen characterization. After minimal but careful sample preparation, the general setup of an MSI experiment involves defining an (x, y) grid over the surface of the sample, with the grid area chosen by the user. The mass spectrometer then ionizes the molecules on the surface of the sample and collects a mass spectrum at each pixel on the section, with the resulting spatial resolution defined by the pixel size. After collecting the spectra, computational software can be used to select an ...

Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights.

Mass spectrometry is being used in many clinical research areas ranging from toxicology to personalized medicine. Of all the mass spectrometry techniques, mass spectrometry imaging (MSI), in particular, has continuously grown towards clinical acceptance. Significant technological and methodological improvements have contributed to enhance the performance of MSI recently, pushing the limits of throughput, spatial resolution, and sensitivity. This has stimulated the spread of MSI usage across various biomedical research areas such as oncology, neurological disorders, cardiology, and rheumatology, just to name a few. After highlighting the latest major developments and applications touching all aspects of translational research (i.e. from early pre-clinical to clinical research), we will discuss the present challenges in translational research performed with MSI: data management and analysis, molecular coverage and identification capabilities, and finally, reproducibility across multiple research centers, which is the largest remaining obstacle in moving MSI towards clinical routine.

Mass spectrometry imaging for clinical research – latest developments, applications, and current limitations

Abnormal choline metabolism continues to be identified in multiple cancers. Molecular causes of abnormal choline metabolism are changes in choline kinase-α, ethanolamine kinase-α, phosphatidylcholi...

/pdf/choline-metabolism-based-molecular-diagnosis-of-cancer-an-3k1ehbpfdt.pdf

Choline metabolism-based molecular diagnosis of cancer: an update

https://pure.rug.nl/ws/files/59838681/1_s2.0_S1936523311800318.pdf

Selecting Potential Targetable Biomarkers for Imaging Purposes in Colorectal Cancer Using TArget Selection Criteria (TASC): A Novel Target Identification Tool

Imaging mass spectrometry (IMS) allows the study of the spatial distribution of small molecules in biological samples. IMS is able to identify and quantify chemicals in situ from whole tissue sections to single cells. Both vacuum mass spectrometry (MS) and ambient MS systems have advanced considerably over the last decade; however, some limitations are still hard to surmount. Sample pretreatment, matrix or solvent choices, and instrument improvement are the key factors that determine the successful application of IMS to different samples and analytes. IMS with innovative MS analyzers, powerful MS spectrum databases, and analysis tools can efficiently dereplicate, identify, and quantify natural products. Moreover, multimodal imaging systems and multiple MS-based systems provide additional structural, chemical, and morphological information and are applied as complementary tools to explore new fields. IMS has been applied to reveal interactions between living organisms at molecular level. Recently, IMS has helped solve many previously unidentifiable relations between bacteria, fungi, plants, animals, and insects. Other significant interactions on the chemical level can also be resolved using expanding IMS techniques. WIREs Syst Biol Med 2017, 9:e1387. doi: 10.1002/wsbm.1387 For further resources related to this article, please visit the WIREs website.

Imaging mass spectrometry for metabolites: technical progress, multimodal imaging, and biological interactions

Mass spectrometric imaging (MSI) in combination with electrospray mass spectrometry (ESI-MS) is a powerful technique for visualization and identification of a variety of different biomolecules directly from thin tissue sections. As commonly used tools for molecular reporting, fluorescent proteins are molecular reporter tools that have enabled the elucidation of a multitude of biological pathways and processes. To combine these two approaches, we have performed targeted MS analysis and MALDI-MSI visualization of a tandem dimer (td)Tomato red fluorescent protein, which was expressed exclusively in the hypoxic regions of a breast tumor xenograft model. For the first time, a fluorescent protein has been visualized by both optical microscopy and MALDI-MSI. Visualization of tdTomato by MALDI-MSI directly from breast tumor tissue sections will allow us to simultaneously detect and subsequently identify novel molecules present in hypoxic regions of the tumor. MS and MALDI-MSI of fluorescent proteins, as exemplified in our study, is useful for studies in which the advantages of MS and MSI will benefit from the combination with molecular approaches that use fluorescent proteins as reporters.

http://link.springer.com/content/pdf/10.1007/s13361-012-0503-y.pdf

FOCUS: DEVELOPMENT AND APPLICATION OF TOF AND TOF/TOF MS: RESEARCH ARTICLE Mass Spectrometric Imaging of Red Fluorescent Protein in Breast Tumor Xenografts

The chemokine receptor CXCR4 and its cognate ligand CXCL12 are pivotal for establishing metastases from many tumor types. Thus, CXCR4 may offer a cell surface target for molecular imaging of metastases, assisting diagnosis, staging, and therapeutic monitoring. Furthermore, noninvasive detection of CXCR4 status of a primary tumor may provide an index of the metastatic potential of the lesion. Here, we report the development and evaluation of [ 64 Cu]AMD3100, a positron-emitting analogue of the stem cell mobilizing agent plerixafor to image CXCR4 in human tumor xenografts preselected for graded expression of this receptor. This imaging method was evaluated in lung metastases derived from human MDA-MB-231 breast cancer cells. Ex vivo biodistribution studies, performed to validate the in vivo imaging data, confirmed the ability of [ 64 Cu] AMD3100 to image CXCR4 expression. Our findings show the feasibility of imaging CXCR4 by positron emission tomography using a clinically approved agent as a molecular scaffold. Cancer Res; 70(10); 3935–44. ©2010 AACR.

Molecular Imaging of CXCR4 Receptor Expression in Human Cancer Xenografts with ( 64 Cu)AMD3100 Positron

Magnetic resonance spectroscopy in investigating the cancer metabolome in preclinical model systems

We report recent advances in ultrathin fiber-optic endomicroscopy technology with significant improvements on resolution and signal collection. Ex vivo and in vivo two-photon imaging of unstained biological tissues and potential clinical applications will be presented.

Scanning nonlinear endomicroscopy technology for intrinsic imaging of biological tissues

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FOCUS: DEVELOPMENT AND APPLICATION OF TOF AND TOF/TOF MS: RESEARCH ARTICLE Mass Spectrometric Imaging of Red Fluorescent Protein in Breast Tumor Xenografts

Molecular Imaging of CXCR4 Receptor Expression in Human Cancer Xenografts with ( 64 Cu)AMD3100 Positron

Magnetic resonance spectroscopy in investigating the cancer metabolome in preclinical model systems

Scanning nonlinear endomicroscopy technology for intrinsic imaging of biological tissues